Rapid DNA binding by nuclear factor kappa B in hepatocytes at the start of liver regeneration.
Rapid DNA binding by nuclear factor kappa B in hepatocytes at the start of liver regeneration.
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发表时间：
1995-04
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通讯作者：
M. Fitzgerald;E. Webber;Justine R. Donovan;N. Fausto
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作者：
M. Fitzgerald;E. Webber;Justine R. Donovan;N. Fausto
三分之二部分肝切除（PH）后的肝脏再生是一个过程，其中静止的、完全分化的肝细胞迅速重新进入细胞周期并最终分裂直至恢复原来的肝脏质量。尽管生长启动信号的确切性质尚不清楚，但在术后第一小时内已检测到生长相关基因的表达增强。这表明转录和转录后调节因子的激活可能是肝再生的一个非常早期的事件。在这里，我们报告了 PH 后 30 分钟内核因子 (NF)-kappa B（p50/p65 异二聚体）和 p50 同二聚体快速、瞬时诱导 DNA 结合。我们还检测到肝切除术后因子的结合。 NF-kappa B 结合在 PH 后 1 小时达到峰值，然后下降，并且不是由假手术诱导的。肝细胞分离研究表明，结合激活发生在肝细胞中，这一结论得到了使用肝细胞系 AML-12 的细胞培养研究的进一步支持。此外，对肝上皮细胞系 LE-6 的研究表明，这些 DNA 结合活性是有丝分裂原诱导的。三分之一肝切除术是一种促使肝细胞对生长因子做出反应的手术，也能诱导 NF-κ B 结合。我们还发现，肿瘤坏死因子 α（可能参与肝再生的控制）在完整动物中快速诱导 NF-κ B DNA 结合活性，类似于 PH 诱导的活性。这些结果表明 NF-κ B 结合可能在使肝细胞具有增殖能力方面发挥作用。
Liver regeneration after two-thirds partial hepatectomy (PH) is a process in which quiescent, fully differentiated hepatocytes rapidly reenter the cell cycle and eventually divide until the original liver mass is restored. Although the exact nature of the growth-initiating signals is unknown, enhanced expression of growth-related genes has been detected during the first hour after operation. This suggests that activation of transcriptional and posttranscriptional regulatory factors is likely to be a very early event in liver regeneration. Here we report the rapid, transient induction of DNA binding by nuclear factor (NF)-kappa B (p50/p65 heterodimer) and p50 homodimers within 30 min after PH. We also detected binding of post-hepatectomy factor. NF-kappa B binding peaks at 1 h after PH before declining and is not induced by sham operation. Liver cell separation studies indicated that the binding activation occurs in hepatocytes, a conclusion further supported by cell culture studies using the hepatocyte cell line AML-12. Furthermore, studies with the liver epithelial cell line LE-6 indicated that these DNA-binding activities are mitogen inducible. One-third hepatectomy, a procedure which primes hepatocytes to respond to growth factors, also induced NF-kappa B binding. We also found that tumor necrosis factor alpha, which may be involved in the control of liver regeneration, rapidly induced NF-kappa B DNA-binding activities in intact animals, similar to those induced by PH. These results suggest that NF-kappa B binding may play a role in making hepatocytes competent to proliferate.